Different types of viruses have been proposed in the art as vector for gene delivery or peptide expression in vivo. In particular, veterinary vaccines have been prepared that express at least one relevant antigen using recombinant viruses such as poxviruses (Ogawa R. et al., Vaccine, 8:486-490 (1990)), adenoviruses (HSU, K. H. et al., Vaccine, 12; 607-612 (1994)), baculoviruses, as well as herpesviruses (Shin, M.-F. et al., Proc. Natl. Acad. Sci. U.S.A., 81:5867-5870 (1984)). Examples of specific virus vectors that permit the expression of a gene for a foreign antigen include Aujeszky's disease virus (pseudorabies virus; PRV) (Van Zijl M. et al., J. Virol., 65:2761-2765 (1991)), herpesvirus of turkey (HVT) (Morgan R. W. et al., Avian Dis. 36:858-870 (1992)), and Marek's disease virus (MDV). Recombinant vectors based on the genus herpesvirus are under intensive study.
There is, however, a need in the art for new viral vector products that can be used to express recombinant peptides or proteins in vivo. In this regard, poxviruses have been engineered to encode different polypeptides. Poxviruses, once released into the blood from infected cells, can infect other cells and thereby potentially lead to elevated expression levels. Recombinant poxviruses have been produced from different types of poxviruses, including cowpox virus, vaccinia virus, and swinepox virus (SPV). So far, however, SPV recombinants have been produced essentially by cloning foreign gene sequences in a genetic region that is considered non-essential for survival of SPV, the TK region (Richard W. Moyer, Eladio Vinuela, E. P. J. Gibbs, U.S. Pat. No. 5,651,972 (1997)).
The inventors of the present invention have now found and validated a novel gene insertion region of SPV into which a variety of foreign gene sequences can be inserted. The resulting recombinant SPV viruses allow efficient and stable expression of the cloned gene sequence, and have large cloning capacity. Furthermore, these viruses have improved immunogenicity in vivo and can be used to produce therapeutics or vaccines for treatment of any mammal, particularly in swine.